NDLI: Epithelial Membrane Protein 2 Controls VEGF Expression in ARPE-19 Cells

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Epithelial Membrane Protein 2 Controls VEGF Expression in ARPE-19 Cells

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Epithelial Membrane Protein 2 Controls VEGF Expression in ARPE-19 Cells

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Telander, David G. Leon, Deanna Forward, Krisztina Wadehra, Madhuri Morales, Shawn A. Braun, Jonathan Gordon, Lynn K.
Description	Country affiliation: United States Author Affiliation: Morales SA ( Department of Ophthalmology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095, USA.)
Abstract	PURPOSE: VEGF production by RPE cells has been shown to be important in regulating aberrant angiogenesis in the retina, which is responsible for multiple types of ocular pathology. EMP2 is highly expressed in the RPE and has been shown to regulate FAK activation, which is implicated in VEGF expression in other cell lines. The purpose of this study was to determine whether EMP2 regulates VEGF expression in the RPE cell line, ARPE-19. METHODS: ARPE-19 cells were engineered to overexpress EMP2. EMP2 siRNA was used to decrease EMP2 expression. The small molecule inhibitor PP2 was used to inhibit FAK activation. VEGF levels were measured by Western blot and ELISA. Functional differences in secreted VEGF were assayed using HUVEC migration. RESULTS: VEGF expression levels correlated with levels of EMP2. An increase of VEGF by 150% was observed in EMP2 overexpressing cells as compared with ARPE-19 cells. Concordantly, EMP2 knockdown resulted in a 57% decrease in VEGF expression. HUVEC migration (P = 0.01) and vessel tube formation (P < 0.01) were significantly increased when exposed to cell culture supernatants from EMP2 overexpressing cells. CONCLUSIONS: This study establishes a novel connection between EMP2 and VEGF and may reflect either a direct effect through the tetraspan web or an indirect change through FAK activation. This connection is functionally significant. In addition to the direct use of anti-VEGF antibodies, modulation of EMP2 with impact on VEGF is potentially a distinct therapeutic target for the treatment of neovascularization associated with retinal diseases that involve pathologic angiogenesis.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.12-11013
Journal	Investigative Opthalmology & Visual Science
Issue Number	3
Volume Number	54
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2013-03-28
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Membrane Glycoproteins Physiology Retinal Pigment Epithelium Metabolism Vascular Endothelial Growth Factor A Blotting, Western Cells, Cultured Enzyme-linked Immunosorbent Assay Focal Adhesion Protein-tyrosine Kinases Antagonists & Inhibitors Gene Expression Regulation Protein Kinase Inhibitors Pharmacology Cytology Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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